Gamma probe and ultrasound-guided fine needle aspiration cytology of the sentinel node (GULF) trial.

PURPOSE: Sentinel lymph node biopsy (SLNB) was introduced as a minimally invasive technique for nodal staging. Since associated morbidity is not negligible, it is highly relevant to pursue a more minimally invasive alternative. The purpose of this study was to prospectively evaluate the sensitivity of fine needle aspiration cytology (FNAC) with combined gamma probe and ultrasound (US) guidance in comparison with the gold standard histology of the sentinel node (SN) after SLNB for detecting metastasis. METHODS: The study was designed as a prospective, multicentre, open-label, single-arm trial enrolling patients with newly diagnosed cutaneous melanoma or breast cancer between May 2015 and August 2017. Sample radioactivity was measured using a Mini 900 scintillation monitor. After FNAC, all patients underwent SLNB. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were estimated. RESULTS: Accrual was terminated early following an unplanned interim analysis indicating that a FNAC sensitivity of at least 80% could not be achieved. In total 58 patients of the originally planned 116 patients underwent FNAC with gamma probe and US guidance. There were no true-positive FNAC results, 14 false-negative results and one false-positive result, and thus the sensitivity, specificity, PPV and NPV of FNAC were 0%, 98%, 0% and 75%, respectively. At least 75% of the FNAC samples had a radioactivity signal higher than the background signal. CONCLUSION: FNAC with gamma probe and US guidance is not able to correctly detect metastases in the SN and is therefore not able to replace SLNB. Gamma probe-guided US is a highly accurate method for correctly identifying the SN, which offers possibilities for future research.

Gamma probe and ultrasound guided fine needle aspiration cytology of the sentinel node (GULF) trial - overview of the literature, pilot and study protocol.

BACKGROUND: Sentinel node (SN) biopsy (SNB) detects clinically occult metastases of breast cancer and melanoma in 20-30%. Wound infections, seroma and lymph edema occur in up to 10%. Targeted ultrasound (US) of the SN, (with fine needle aspiration cytology (FNAC) if appropriate) has been investigated as a minimally invasive alternative, but reported sensitivity rates are too low to replace SNB. Our hypothesis is that the use of a handheld gamma probe concomitant with US may improve sensitivity. Our aim is to provide an overview of the current literature on preoperative nodal staging of clinical N0 melanoma patients, report on a pilot, and present a study protocol for a minimally invasive alternative to the SNB: Gamma probe and Ultrasound guided Fine needle aspiration cytology of the sentinel node (GULF trial). METHODS: The GULF trial is a multicenter open single arm observational trial. Newly diagnosed cT1b-4N0M0 cutaneous melanoma or cT1-3N0M0 breast cancer patients, aged >18 years, presenting for SNB are eligible. 120 patients will be included for preoperative targeted gamma probe guided US and FNAC of the SN. Afterwards all patients proceed to surgical SNB. Primary endpoint is the sensitivity of FNAC. Secondary endpoints include SN identification rate and the histopathological compatibility of Core Needle Biopsy and FNAC vs. SNB. Secondary endpoints were investigated in a pilot with 10 FNACs and marker placements, and 10 FNACs combined with Core Needle Biopsy. RESULTS: A pilot in 20 patients showed that SN identification rate was 90%, supporting the feasibility of this technique. DISCUSSION: There is broad experience with US (in combination with FNAC) prior to SNB, but sensitivity and specificity are too low to completely abandon SNB. Promising alternative techniques potentially will replace SNB in the future but more evidence is needed in the form of prospective studies. Accurate identification of the SN for US-FNAC has been proven feasible in our pilot. When adequate sensitivity can be reached, US-FNAC provides a minimally invasive alternative for the surgical SNB procedure. TRIAL REGISTRATION: The GULF trial is registered in the Netherlands Trial Registry (NTR), ID: NRT5193 . May 1st 2015.